The Efficacy of Darolutamide for Non Metastatic Castration-Resistant Prostate Patients

Neal Shore | January 20, 2020

In July 2019, darolutamide became the newest available oral androgen receptor inhibitor approved by the FDA for the treatment of nonmetastatic castration-resistant prostate cancer (nmCRPC) patients. The Phase 3 ARAMIS trial evaluated darolutamide with androgen deprivation therapy (ADT) versus ADT plus placebo for nmCRPC patients and demonstrated significant improvement in metastasis-free survival (MFS), extending MFS to 40 months for those treated with darolutamide as opposed to 18 months for patients randomized to the ADT + placebo arm.

Novel approaches for the treatment of nmCRPC are now NCCN recommended, as the preferred approach to thwart prostate cancer progression for nmCRPC patients. With the awareness of a rising PSA with castrate levels of testosterone, and a lack of metastases with CT and Bone scan imaging, novel oral AR inhibitors will improve MFS., thus the importance of routine and appropriate PSA monitoring with attendant radiographic imaging. Darolutamide’s approval, licensed with the commercial name, Nubeqa, provides the arrival of another important therapeutic option for extending MFS in nmCRPC patients.


Neal Shore, MD, FACS

Neal D. Shore, MD, FACS is the Medical Director for the Carolina Urologic Research Center. He practices with Atlantic Urology Clinics in Myrtle Beach, South Carolina. Dr. Shore has conducted more than 350 clinical trials, focusing mainly on GU Oncology, and serves on the Executive Boards of: Society of Urologic Oncology Board, Bladder Cancer Advocacy Network, and is Immediate Past President, Large Urology Group Practice Association. He is a founder for both: CUSP Clinical Trials Consortium, as well as for DASHKO, large urology practices data registries. He serves as the National Urology Research Director for 21st Century Oncology. He has served on the AUA Male Health Committee and the AUA Data Committee, the SITC Task Force for Prostate Cancer, the Bladder Cancer Advocacy Think Tank and the editorial boards of Reviews in Urology, Urology Times, Chemotherapy Advisor, OncLive, PLOS ONE (Academic Editor), Urology Practice, World Journal of Urology, and serves as Editor, Everyday Urology-Oncology. He has more than 200 peer-reviewed publications and numerous book chapters; he performs peer review for Lancet Oncology, New England Journal of Medicine, European Urology, Journal Urology, Urology, BJUI, PCPD, and numerous other high impact scientific journals. A graduate of Duke University and Duke University Medical School, Dr. Shore completed a 6-month clinical research fellowship in Pretoria, South Africa, and then completed his General Surgery/Urology training at New York Hospital Cornell Medical Center and at Memorial Sloan-Kettering Cancer Center in New York City. He is a Fellow of the American College of Surgeons.

Clinical Conversations by Experts
Everyday Urology - Oncology Insights
Publications focusing on urologic cancer treatments through original manuscripts
By Neal Shore
Patients with non-metastatic castration-resistant prostate cancer (nmCRPC, formerly known as M0 CRPC) have rising prostate-specific antigen (PSA) levels despite castrate levels of testosterone with approved androgen deprivation therapy (ADT) and no detectable metastases on conventional imaging with computed tomography (CT) and bone scans.1
By Neal Shore, MD

Published Date: September 2019

Androgen deprivation therapy (ADT) is the longstanding initial treatment for advanced hormone-sensitive prostate adenocarcinoma. Nonetheless, patients who are initiated on ADT will invariably progress by developing prostate cancer cellular clonal populations, which creates a phenotype of more castration-resistant disease with more aggressive biology.1

By Stephen B. Williams, MD and Ashish M. Kamat, MD, MBBS

Published Date: June 2017

When patients receive a diagnosis of cancer it can be devastating. Suddenly their world is turned upside down, populated by doctors, diagnostic tests, and treatments.

The standard process for newly diagnosed patients with prostate cancer is a chronologically linear and often one-dimensional process managed by urologists.3

Library Resources
The State-of-the-Evidence in Brief Reviews by Experts
Written by Christopher J.D. Wallis, MD, PhD and Zachary Klaassen, MD, MSc
September 17, 2020
While there have been dramatic changes in treatment options for patients with advanced prostate cancer over the past 5 years, perhaps the greatest change has been for patients with non-metastatic castration-resistant prostate cancer (nmCRPC). Prior to February 14, 2018, there were no agents approved by the United States Food and Drug Administration (FDA) for men with nmCRPC.
Written by Jeanny B. Aragon-Ching, M.D., F.A.C.P.
May 15, 2020
Darolutamide is a novel anti-androgen that is recently approved for men with non-metastatic castration-resistant prostate cancer. Darolutamide is structurally different from the previously discovered androgen receptor (AR) agents enzalutamide, bicalutamide and apalutamide. Early phase trials showed promising results with overall safety profiles that are generally well-tolerated.
Written by Zachary Klaassen, MD, MSc and Christopher J.D. Wallis, MD, PhD
April 16, 2019
Over the last two or more years, the treatment of men with M0 CRPC has drastically changed, most recently with the approval of darolutamide in this disease space based on data from the ARAMIS trial. The objective of this article is to provide a contemporary review of treatment options for men with non-metastatic CRPC.
Conference Coverage
Conference Highlights from Recent Conference Coverage
Presented by Alicia Morgans, MD, MPH 
In a stand-alone session at this year’s Society of Urologic Oncology (SUO) virtual annual meeting, titled Understanding the Evolving Treatment Landscape in Prostate Cancer: How to Leverage the Latest Advances and Strategies to Optimize Patient Outcomes,
Presented by Karim Fizazi, MD, Ph.D.
There has been a rapid evolution in treatment options for patients with non-metastatic castration-resistant prostate cancer (nmCRPC) since the spring of 2018. Up until the presentation of SPARTAN and PROSPER trials, reporting on the use of apalutamide and enzalutamide in non-metastatic castration-resistant prostate cancer, at GU ASCO in February 2018, there were no specifically approved treatment options for these patients.
Presented by Karim Fizazi, MD, PhD
There has been a rapid evolution in treatment options for patients with non-metastatic castration-resistant prostate cancer since the spring of 2018. Up until the presentation of SPARTAN and PROSPER trials, reporting on the use of apalutamide and enzalutamide in non-metastatic castration-resistant prostate cancer, at GU ASCO in February 2018, there were no specifically approved treatment options for these patients.
Presented by Karim Fizazi, MD, Ph.D.
Darolutamide is a unique androgen receptor inhibitor, FDA approved in July 2019 for the treatment of non-metastatic castration-resistant prostate cancer. This approval was based on ARAMIS,1 a large multicenter double-blind, placebo-controlled study that randomized 1500 patients to 600 milligrams of darolutamide twice a day or placebo.
Presented by Boris Hadaschik, MD
Athens, Greece ( Dr. Boris Hadaschik presented on the disease entity of non-metastatic castrate-resistant prostate cancer (nmCRPC).
Presented by Matthew R. Smith, MD, PhD
Barcelona, Spain ( The randomized, phase 3 SPARTAN trial showed that apalutamide offered a metastasis-free survival (MFS) benefit over placebo for patients with non-metastatic
Presented by Christopher Parker, MD
Barcelona, Spain ( The optimal timing of radiotherapy after radical prostatectomy for prostate cancer is uncertain. Supporters of adjuvant radiotherapy suggest that earlier treatment may be more effective,
Presented by Matthew R. Smith, MD, PhD
Barcelona, Spain ( In the phase III placebo-controlled SPARTAN study, apalutamide with ongoing androgen deprivation therapy (ADT) significantly improved metastasis-free survival (MFS) (HR 0.28, 95% CI, 0.23-0.35),
Presented by Teuvo Tammela, MD, PhD
Barcelona, Spain (  Dr. Teuvo Tammela presented results of the recently published ARAMIS trial. Non-metastatic (M0) CRPC (nmCRPC) is defined as a rising PSA in the setting of non-metastatic disease in the castrate state.
Presented by Karim Fizazi, MD, PhD
San Francisco, CA ( The use of androgen-axis targeted agents, specifically enzalutamide and abiraterone, have drastically changed the landscape of advanced prostate cancer management. Just last year, at GU ASCO 2018,
Presented by Neil Fleshner, MD, MPH, FRCSC
Toronto, Ontario ( Dr. Neil Fleshner presented the question in debate of whether we should be treating non-metastatic castrate-resistant prostate cancer (nmCRPC) patients or wait until they have developed metastases.
Presented by Maha Hussain, MD, FACP, FASCO
San Francisco, CA ( Dr. Maha Hussain provided the first presentation of the phase III randomized double-blind controlled trial, the following men were eligible for inclusion